Genetic Epidemiology, Translational Neurogenomics, Psychiatric Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
25201988
TITLE
Common genetic variants associated with cognitive performance identified using the proxy-phenotype method.
ABSTRACT
We identify common genetic variants associated with cognitive performance using a two-stage approach, which we call the proxy-phenotype method. First, we conduct a genome-wide association study of educational attainment in a large sample (n = 106,736), which produces a set of 69 education-associated SNPs. Second, using independent samples (n = 24,189), we measure the association of these education-associated SNPs with cognitive performance. Three SNPs (rs1487441, rs7923609, and rs2721173) are significantly associated with cognitive performance after correction for multiple hypothesis testing. In an independent sample of older Americans (n = 8,652), we also show that a polygenic score derived from the education-associated SNPs is associated with memory and absence of dementia. Convergent evidence from a set of bioinformatics analyses implicates four specific genes (KNCMA1, NRXN1, POU2F3, and SCRT). All of these genes are associated with a particular neurotransmitter pathway involved in synaptic plasticity, the main cellular mechanism for learning and memory.
DATE PUBLISHED
2014 Sep 23
HISTORY
PUBSTATUS PUBSTATUSDATE
entrez 2014/09/10 06:00
pubmed 2014/09/10 06:00
medline 2015/04/23 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Rietveld CA Rietveld Cornelius A CA Department of Applied Economics, Erasmus School of Economics, Erasmus University, 3000 DR, Rotterdam, The Netherlands; Departments of Epidemiology.
Esko T Esko Tõnu T Division of Genetics and Endocrinology, Boston Children's Hospital, Boston, MA 02115; Program in Medical and Population Genetics, Broad Institute of the Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142; Department of Genetics, Harvard Medical School, Boston, MA 02115; Estonian Genome Center, University of Tartu, 51010 Tartu, Estonia;
Davies G Davies Gail G Centre for Cognitive Ageing and Cognitive Epidemiology, Department of Psychology, and.
Pers TH Pers Tune H TH Division of Genetics and Endocrinology, Boston Children's Hospital, Boston, MA 02115; Program in Medical and Population Genetics, Broad Institute of the Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142;
Turley P Turley Patrick P Departments of Economics and.
Benyamin B Benyamin Beben B Queensland Brain Institute, University of Queensland, Brisbane, QLD 4072, Australia;
Chabris CF Chabris Christopher F CF Department of Psychology, Union College, Schenectady, NY 12308;
Emilsson V Emilsson Valur V Icelandic Heart Association, 201 Kopavogur, Iceland; Faculty of Pharmaceutical Sciences, University of Iceland, 107 Reykjavík, Iceland;
Johnson AD Johnson Andrew D AD Framingham Heart Study, National Heart, Lung, and Blood Institute, Framingham, MA 01702;
Lee JJ Lee James J JJ Psychology, Harvard University, Cambridge, MA 02138; Department of Psychology, University of Minnesota, Minneapolis, MN 55455-0344;
de Leeuw C de Leeuw Christiaan C Department of Complex Trait Genetics, VU University Amsterdam and VU Medical Center, 1081 HV, Amsterdam, The Netherlands; Machine Learning Group, Intelligent Systems, Institute for Computing and Information Sciences, Faculty of Science, Radboud University, 6500 GL, Nijmegen, The Netherlands;
Marioni RE Marioni Riccardo E RE Centre for Cognitive Ageing and Cognitive Epidemiology, Queensland Brain Institute, University of Queensland, Brisbane, QLD 4072, Australia; Centre for Genomic and Experimental Medicine and.
Medland SE Medland Sarah E SE Quantitative Genetics Laboratory, QIMR Berghofer Medical Research Institute, Brisbane, QLD 4029, Australia;
Miller MB Miller Michael B MB Department of Psychology, University of Minnesota, Minneapolis, MN 55455-0344;
Rostapshova O Rostapshova Olga O Harvard Kennedy School, Harvard University, Cambridge, MA 02139;
van der Lee SJ van der Lee Sven J SJ Genetic Epidemiology Unit, Department of Epidemiology and Biostatistics, and.
Vinkhuyzen AA Vinkhuyzen Anna A E AA Queensland Brain Institute, University of Queensland, Brisbane, QLD 4072, Australia;
Amin N Amin Najaf N Genetic Epidemiology Unit, Department of Epidemiology and Biostatistics, and.
Conley D Conley Dalton D Department of Sociology and.
Derringer J Derringer Jaime J Department of Psychology, University of Illinois, Urbana-Champaign, IL 61820;
van Duijn CM van Duijn Cornelia M CM Genetic Epidemiology Unit, Department of Epidemiology and Biostatistics, and Centre for Medical Systems Biology, Leiden University Medical Center, 2300 RC, Leiden, The Netherlands;
Fehrmann R Fehrmann Rudolf R Department of Genetics, University Medical Center Groningen, University of Groningen, 9713 GZ, Groningen, The Netherlands;
Franke L Franke Lude L Department of Genetics, University Medical Center Groningen, University of Groningen, 9713 GZ, Groningen, The Netherlands;
Glaeser EL Glaeser Edward L EL Departments of Economics and.
Hansell NK Hansell Narelle K NK Neuroimaging Genetics Group, QIMR Berghofer Medical Research Institute, Brisbane, QLD 4029, Australia;
Hayward C Hayward Caroline C Centre for Genomic and Experimental Medicine and Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, United Kingdom;
Iacono WG Iacono William G WG Department of Psychology, University of Minnesota, Minneapolis, MN 55455-0344;
Ibrahim-Verbaas C Ibrahim-Verbaas Carla C Harvard Kennedy School, Harvard University, Cambridge, MA 02139; Neurology, and.
Jaddoe V Jaddoe Vincent V Departments of Epidemiology, Generation R Study Group, Erasmus Medical Center, 3000 CA, Rotterdam, The Netherlands;
Karjalainen J Karjalainen Juha J Department of Genetics, University Medical Center Groningen, University of Groningen, 9713 GZ, Groningen, The Netherlands;
Laibson D Laibson David D Departments of Economics and.
Lichtenstein P Lichtenstein Paul P Departments of Economics and.
Liewald DC Liewald David C DC Centre for Cognitive Ageing and Cognitive Epidemiology.
Magnusson PK Magnusson Patrik K E PK Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, 171 77 Stockholm, Sweden;
Martin NG Martin Nicholas G NG Genetic Epidemiology Laboratory, QIMR Berghofer Medical Research Institute, Brisbane, QLD 4029, Australia;
McGue M McGue Matt M Department of Psychology, University of Minnesota, Minneapolis, MN 55455-0344;
McMahon G McMahon George G School of Social and Community Medicine, University of Bristol, Bristol BS8 2PR, United Kingdom;
Pedersen NL Pedersen Nancy L NL Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, 171 77 Stockholm, Sweden;
Pinker S Pinker Steven S Psychology, Harvard University, Cambridge, MA 02138;
Porteous DJ Porteous David J DJ Centre for Cognitive Ageing and Cognitive Epidemiology, Centre for Genomic and Experimental Medicine and.
Posthuma D Posthuma Danielle D Department of Complex Trait Genetics, VU University Amsterdam and VU Medical Center, 1081 HV, Amsterdam, The Netherlands; Department of Child and Adolescent Psychiatry, Erasmus Medical Center, 3000 CB, Rotterdam, The Netherlands; Department of Clinical Genetics, VU University Medical Center, 1081 BT, Amsterdam, The Netherlands;
Rivadeneira F Rivadeneira Fernando F Departments of Epidemiology, Internal Medicine.
Smith BH Smith Blair H BH Medical Research Institute, University of Dundee, Dundee DD2 4RB, United Kingdom;
Starr JM Starr John M JM Centre for Cognitive Ageing and Cognitive Epidemiology, Alzheimer Scotland Dementia Research Centre, University of Edinburgh, Edinburgh EH8 9JZ, United Kingdom;
Tiemeier H Tiemeier Henning H Departments of Epidemiology, Department of Child and Adolescent Psychiatry, Erasmus Medical Center, 3000 CB, Rotterdam, The Netherlands;
Timpson NJ Timpson Nicholas J NJ Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol BS8 2PR, United Kingdom;
Trzaskowski M Trzaskowski Maciej M Medical Research Council Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, London SE5 8AF, United Kingdom;
Uitterlinden AG Uitterlinden André G AG Departments of Epidemiology, Internal Medicine.
Verhulst FC Verhulst Frank C FC Department of Child and Adolescent Psychiatry, Erasmus Medical Center, 3000 CB, Rotterdam, The Netherlands;
Ward ME Ward Mary E ME School of Social and Community Medicine, University of Bristol, Bristol BS8 2PR, United Kingdom;
Wright MJ Wright Margaret J MJ Neuroimaging Genetics Group, QIMR Berghofer Medical Research Institute, Brisbane, QLD 4029, Australia;
Davey Smith G Davey Smith George G Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol BS8 2PR, United Kingdom;
Deary IJ Deary Ian J IJ Centre for Cognitive Ageing and Cognitive Epidemiology, Department of Psychology, and.
Johannesson M Johannesson Magnus M Department of Economics, Stockholm School of Economics, 113 83 Stockholm, Sweden;
Plomin R Plomin Robert R Medical Research Council Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, London SE5 8AF, United Kingdom;
Visscher PM Visscher Peter M PM Queensland Brain Institute, University of Queensland, Brisbane, QLD 4072, Australia; University of Queensland Diamantina Institute, University of Queensland, Princess Alexandra Hospital, Brisbane, QLD 4102, Australia;
Benjamin DJ Benjamin Daniel J DJ Department of Economics, Cornell University, Ithaca, NY 14853; daniel.benjamin@gmail.com p.d.koellinger@uva.nl.
Cesarini D Cesarini David D Center for Experimental Social Science, Department of Economics, New York University, New York, NY 10012; Institute for the Interdisciplinary Study of Decision Making, New York University, New York, NY 10012; and daniel.benjamin@gmail.com p.d.koellinger@uva.nl.
Koellinger PD Koellinger Philipp D PD Department of Applied Economics, Erasmus School of Economics, Erasmus University, 3000 DR, Rotterdam, The Netherlands; Departments of Epidemiology, Faculty of Economics and Business, University of Amsterdam, 1012 WX, Amsterdam, The Netherlands daniel.benjamin@gmail.com p.d.koellinger@uva.nl.
INVESTIGATORS
JOURNAL
VOLUME: 111
ISSUE: 38
TITLE: Proceedings of the National Academy of Sciences of the United States of America
ISOABBREVIATION: Proc Natl Acad Sci U S A
YEAR: 2014
MONTH: Sep
DAY: 23
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1091-6490
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Proc Natl Acad Sci U S A
COUNTRY: United States
ISSNLINKING: 0027-8424
NLMUNIQUEID: 7505876
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Meta-Analysis
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
ErratumIn Proc Natl Acad Sci U S A. 2015 Jan 27;112(4):E380 25572966
GRANTS
GRANTID AGENCY COUNTRY
R37 AA009367 NIAAA NIH HHS United States
MC_UU_12013/3 Medical Research Council United Kingdom
P30AG012810 NIA NIH HHS United States
R01 AA011886 NIAAA NIH HHS United States
R24 HD047879 NICHD NIH HHS United States
MC_PC_15018 Medical Research Council United Kingdom
R01 DA024417 NIDA NIH HHS United States
MC_UU_12013/1 Medical Research Council United Kingdom
T32 MH016880 NIMH NIH HHS United States
P01AG005842 NIA NIH HHS United States
G0500079 Medical Research Council United Kingdom
R37 DA005147 NIDA NIH HHS United States
ETM/55 Chief Scientist Office United Kingdom
CZB/4/505 Chief Scientist Office United Kingdom
MR/K026992/1 Medical Research Council United Kingdom
G0901245 Medical Research Council United Kingdom
102215 Wellcome Trust United Kingdom
R01 MH066140 NIMH NIH HHS United States
CZD/16/6/4 Chief Scientist Office United Kingdom
MC_PC_U127561128 Medical Research Council United Kingdom
T32AG000186-23 NIA NIH HHS United States
F31 DA029377 NIDA NIH HHS United States
BB/F019394/1 Biotechnology and Biological Sciences Research Council United Kingdom
P01 AG005842 NIA NIH HHS United States
P30 AG012810 NIA NIH HHS United States
T32 AG000186 NIA NIH HHS United States
P01AG005842-20S2 NIA NIH HHS United States
G9815508 Medical Research Council United Kingdom
R01 DA013240 NIDA NIH HHS United States
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Calcium-Binding Proteins
Cell Adhesion Molecules, Neuronal genetics
Cognition physiology
Female physiology
Humans physiology
Learning physiology
Male physiology
Memory physiology
Multifactorial Inheritance physiology
Nerve Tissue Proteins genetics
Neural Cell Adhesion Molecules genetics
Neuronal Plasticity genetics
Octamer Transcription Factors genetics
Polymorphism, Single Nucleotide genetics
Synaptic Transmission genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
0 Calcium-Binding Proteins
0 Cell Adhesion Molecules, Neuronal
0 NRXN1 protein, human
0 Nerve Tissue Proteins
0 Neural Cell Adhesion Molecules
0 Octamer Transcription Factors
0 POU2F3 protein, human
OTHER ID's
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